CONTENTS
I | |
| Contents: Introductory. Earliest period. Francis Glisson as founderof the doctrine of irritability. Albrecht von Haller. The vitalists.Bordeu and Barthez. John Brown’s system. Johannes Müllerand the specific energy of living substance. Rudolf Virchow’sdoctrine of the irritability of the cell. Discovery of the inhibitoryeffects of stimulation. Weber, Schiff, Goltz, Setschenow, Sherrington.Claude Bernard studies on narcosis. Tropisms. Ehrenberg,Engelmann, Pfeffer, Strassburger, Stahl. Semon’s speculationson mneme. | |
II | |
| Contents: Principles of scientific knowledge and research. Originand meaning of the conception of cause. Cause and condition.Criticism of the conception of cause. The conditional point ofview. Conception of cause. The conditional point of view appliedto the investigation of life. Conception of vital conditions. Definitionof the conception of stimulation. | |
III | |
| Contents: The quality of the stimulus. Positive and negative alterationsof the factors which act as vital conditions. Extent of thealteration in vital conditions or intensity of the stimulus. Thresholdstimuli, sub-threshold, submaximal, maximal and supermaximalintensities of stimulus. Relations between the intensity ofstimulus and the amount of response. The Weber and Fechnerlaw. All or none law. Time relations of the course of thestimulus. Form of individual stimulus. Absolute and relativerapidity in the course of the stimulus. Duration of the stimulusafter reaching its highest point. Adaptation to persistent stimuli.Series of individual stimuli. Rhythmical stimuli. The Nernstlaw. | |
IV | |
| Contents: Various examples of the effects of stimulation. Metabolismof rest and metabolism of stimulation. Metabolic equilibrium,Disturbances of equilibrium by stimuli. Quantitative andqualitative alterations of the metabolism of rest under the influenceof stimuli. Excitation and depression. Specific energy ofliving substance. Qualitative alterations of the specific metabolismand their relations to pathology. Functional and cytoplasticstimuli. Relations of the cytoplastic effects of stimuli to the functional.Hypertrophy of activity and atrophy of inactivity. Metabolicalterations during growth of the cell. Primary and secondaryeffects of stimulation. Scheme of effects of stimulation. | |
V | |
| Contents: Indicators for the investigation of the process of excitation.Latent period. The question of the existence of assimilatory excitations.Dissimilatory excitations. Excitations of the partialcomponents of functional metabolism. Production of energy inthe chemical splitting up processes. Oxydative and anoxydativedisintegration. Theory of oxydative disintegration. Dependenceof irritability on oxygen. Experiments on unicellular organisms,nerve centers and nerve fibers. Restitution after disintegration bymetabolic self-regulation. Organic reserve supplies of the cell.The question of a reserve supply of oxygen of the cell. Metabolicself-regulation as a form of the law of mass effect, and metabolicequilibrium as a condition of chemical equilibrium. Functionalhypertrophy. | |
VI | |
| Contents: Only processes of excitation are conducted, not processes ofdepression. Conduction of excitation in its two extreme instances.Conduction in undifferentiated pseudopod protoplasm of rhizopoda.Conduction of excitation with decrement of intensity and rapidity.Conduction of excitation in the nerve. Rapidity of conduction.Conduction of excitation without decrement. Relation betweenirritability and conductivity. Conduction of excitation with decrementof the nerve after artificial depression of irritability by narcosis.Theory of the decrementless conduction of the normalnerve. Proof of the validity of the “all or none law” in themedullated nerve. Theory of the process of the conductivity ofexcitation. Theory of core model (Kernleiter). Electrochemicaltheory of conduction based on the properties of semi-permeablesurfaces. | |
VII | |
| Contents: Conception of specific irritability. Alteration of specificirritability during and after excitation. Refractory period invarious forms of living substance. Absolute and relative refractoryperiod. Curve of irritability during refractory period.Dependence of the duration of the refractory period on therapidity of the course of the metabolic processes in the livingsubstance. Dependence on temperature. Dependence on supplyof oxygen. Theory of refractory period. Refractory period asbasis of fatigue. Fatigue as a form of asphyxiation. Alterationsof irritability and the course of excitation in fatigue. Recoveryfrom fatigue. The rôle played by oxygen in recovery. Fatigueas an expression of the prolongation of the refractory periodconditioned by the relative want of oxygen. Fatigue of the nerve. | |
VIII | |
| Contents: Examples of effects of interference of stimuli in unicellularorganisms. Interference of galvanic and thermic stimuli in Paramecia.Interference of galvanic and thermic stimuli and narcotics.Interference of galvanic and mechanical stimuli. Interference ofgalvanotaxis and thigmotaxis in Paramecia and hypotin infusoria.Real or homotop interference, apparent or heterotop interference.The two effects of homotop interference of excitations: Summationand inhibition of excitations. Theory of the processes ofinhibition. Hering-Gaskell Theory. Inhibition as an expressionof the refractory period. Individual possibilities of interferenceof two stimuli. Interference of an excitating and a depressingstimulus. Interference of two depressing stimuli. Interferenceof two excitating stimuli. Analysis of the interference of twoexcitations. Interference of two single stimuli. Conditions uponwhich the result of interference is dependent. Heterobole andisobole living systems. Intensity of the two stimuli. Intervalbetween the stimuli. Specific irritability and rapidity of reactionof the living system. Latent period. Interference of single stimuliin a series. General scheme of the development of the effectof interference. Summation and inhibition. Apparent increase ofirritability. Conditions of summation. Tonic excitations. Conditionsof inhibitions. Various types of inhibition. Interference oftwo series of stimuli. Relations in the nervous system. Peculiaritiesof the nerve fibers. Conversion of the nerve by relativefatigue from an isobolic into a heterobolic system. | |
IX | |
| Contents: Necessity of cellular physiological analysis of toxic depressionsby pharmacology. Apparent variety of processes of depression.Depression of oxydative disintegration as the most extendedprinciple in the processes of depression. Asphyxiation, fatigue,heat depression, as a consequence of restriction of oxydative disintegration.Narcosis. Theories of narcosis. The alteration ofspecific irritability and conductivity in narcosis. Depression ofoxydative processes in narcosis. Asphyxiation of living substancewhen oxygen is present during narcosis. Persistence of anoxydativedisintegration in narcosis. Increase of the same by stimuli.Depression by narcosis as a form of acute asphyxiation. Hypothesison the mechanism of depression of oxygen exchange by narcotics.Possibility of combining the facts with the observations ofMeyer and Overton. |
IRRITABILITY
CHAPTER I
THE HISTORY OF THE SUBJECT
Contents: Introductory. Earliest period. Francis Glisson as founder of the doctrine of irritability. Albrecht von Haller. The vitalists. Bordeu and Barthez. John Brown’s system. Johannes Müller and the specific energy of living substance. Rudolf Virchow’s doctrine of the irritability of the cell. Discovery of the inhibitory effects of stimulation. Weber, Schiff, Goltz, Setschenow, Sherrington. Claude Bernard studies on narcosis. Tropisms. Ehrenberg, Engelmann, Pfeffer, Strassburger, Stahl. Semon’s speculations on mneme.
Irritability is a general property of living substance but not exclusively so. Irritable systems also exist in inanimate nature. What characterizes living substances is not irritability as such, but an irritability of a specific type. The irritability of the living system can, therefore, not be studied alone, but as the properties of a living system are dependent upon each other, so this property must be considered with the others possessed by a living substance. In this sense irritability presents a problem of fundamental physiological importance. For if we could analyze the irritability of living substance to its essence, then the nature of life itself would be fathomed. The analysis of irritability of living substance offers us, therefore, a path to the investigation of life and herein lies the importance of the study of irritability.
I wish to follow this path toward the knowledge of the vital processes and to endeavor to show in these lectures what information the analysis of irritability and that of the effect of stimuli can give us of the mechanism of the processes in living substance. Before doing so, however, I wish to consider somewhat more in detail the question as to how we have arrived at the conception of the nature of irritability.
To the thinkers both in the field of physiology and medicine of ancient and mediæval times the conception of irritability was quite foreign. Even a comprehension of the nature of stimuli had not yet begun to crystallize from vague impressions of the various influences of different agents on the human being. Nevertheless they knew of such influences of the most varying kinds upon the human body. The ancients already possessed a materia medica, founded on the real or supposed influence of various mineral, vegetable and animal substances upon the organism. It was also known that heat and cold, light and darkness had an effect upon disease. They likewise believed in the influence of certain factors upon the health of man, which in reality have no effect whatsoever, as the stars and the magnet. But neither in ancient nor in mediæval times was the state of knowledge reached wherein generalizations were made from these agents, which had a real or supposed action upon the organism, and to combine these to a general conception of stimulation.
The conception of stimulation and irritability cannot however be separated.
The founder of the doctrine of the irritability of living substance is Francis Glisson (1597–1677), member of the Collegium Medicum in London and at the same time Professor in Cambridge. It is a fact also not altogether without interest, that Glisson at the same time was in a certain sense a forerunner of those who interpreted nature from a physical standpoint. Glisson as an anatomist and physiologist was an excellent observer and experimenter, but the most prominent trait of his character was his inclination to philosophic observation and analysis of nature. His “Tractatus de natura substantiæ energetica”[1] must, therefore, be considered as the chief work of his life. In this voluminous book Glisson develops an entire system of natural philosophy, which in accord with the character of the philosophy of that time is unfortunately of an absolutely speculative nature and which had hardly emancipated itself from the scholasticism of the preceding period of thought. When the ideas of Glisson are isolated from the wilderness of scholastic phraseology, the system is somewhat as follows. The basis of all existence, “substance,” has according to him two general properties, its “fundamental subsistence,” that is, the essence of its being, and its “energetic subsistence,” that is, the essence of its activity. To these are added the properties possessed in specific cases, that is, its “additional subsistence.” The energetic subsistence forms the basis of all life. Life is therefore present not only in organic nature, but in all nature which is characterized by the union of the general energetic subsistence with the special additional subsistence of an animal and vegetable nature. In other forms of life in nature the energetic subsistence is combined with other special forms of the additional subsistence. The universal essence of all life, that is the energetic subsistence, has only three fundamental faculties: the “appetitiva,” the “perceptiva” and the “motiva.” The modus is the result of a “perceptio,” but the “perceptio” is not thinkable unless the object has the “appetitus” to receive the external influence. Glisson’s doctrine of irritability is based on this conception, which he develops in a second work already begun before the “Tractatus de natura substantiæ,” but not finished until later and only published after his death. In this “Tractatus de ventriculo et intestinis,”[2] Glisson dwells in detail on the physiological properties of animal structures and develops for the first time his conception of irritability in the chapter “De irritabilitate fibrarum.” The “irritability” manifests itself in the appearance of the alteration of movement, which is brought about by external influences on the animal structure, for: “Motiva fibrarum facultas nisi irritabilis foret, vel, perpetuo quiesceret, vel perpetuo idem ageret.” The fundamental factor of this irritability Glisson attributes to the “perceptio,” which he distinguishes as a “perceptio naturalis, sensitiva and animalis.” The want of clearness produced here by Glisson’s artificial distinctions and mode of expression is in part removed if we endeavor to transfer his meaning into our present methods of thought. This distinction would then simply point out the different means by which the stimuli can reach the irritable structures. The “Perceptio naturalis” is that which today we should call “direct response” to stimulation, that is, the excitation of the fiber by artificial stimuli applied directly to the tissue. Glisson shows here, that the intestines and muscles in the body immediately after death and even when removed from the body can be stimulated to movement by means of corrosive fluids or cold. The “Perceptio sensitiva” is, according to Glisson, the excitation of the fibers by external stimuli which act on the intact body as a whole by way of the sensory nerves. The “Perceptio ab appetitu animali regulata” finally is the excitation by inner stimuli proceeding from the brain. The Perceptio naturalis is possessed by all parts of the body, even the fluids, the bones and the fat. All of them are irritable. But a “vitale” and a special “animal” irritability they do not possess to a perceptible degree. These forms of irritability belong only to the special parts of the body. Here, however, the distinctions made by Glisson, are quite vague and contradictory. In his “Tractatus de ventriculo et intestinis” Glisson sharply distinguishes the “sensatio” from the “perceptio.” The perceptio in itself is not a sensation, for although individual organs of the body are irritable, as they all possess a “perceptio,” they are not in themselves sensitive. The “sensatio,” the sensation, only arises when the external “perceptio” of the individual organs combine through the nerves with the internal “perceptio” of the brain. “Nisi enim percepto externa ab interna simul percipiatur, non est cognitio sensitiva completa.” Sensitivity is, therefore, a special faculty, that is only based upon irritability.